This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Louie, T.
Right arrow Articles by Goldstein, E. J. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Louie, T.
Right arrow Articles by Goldstein, E. J. C.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, January 2009, p. 223-228, Vol. 53, No. 1
0066-4804/09/$08.00+0     doi:10.1128/AAC.01442-07
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Clinical Outcomes, Safety, and Pharmacokinetics of OPT-80 in a Phase 2 Trial with Patients with Clostridium difficile Infection{triangledown}

T. Louie,1* M. Miller,2 C. Donskey,3 K. Mullane,4 and E. J. C. Goldstein5

University of Calgary, Calgary, Alberta, Canada,1 Jewish General Hospital, Montreal, Quebec, Canada,2 VA Medical Center, Cleveland, Ohio,3 University of Chicago, Chicago, Illinois,4 R. M. Alden Research Laboratory, Santa Monica, California5

Received 6 November 2007/ Returned for modification 2 May 2008/ Accepted 17 October 2008

OPT-80, a novel, minimally absorbed macrocycle, is a candidate treatment option for Clostridium difficile infection (CDI) based on cure without recurrence of CDI in the hamster challenge model, good in vitro activity against C. difficile, and relative sparing of commensal gram-negative anaerobes. In this open-label, dose-ranging clinical trial, 48 evaluable subjects were randomized to receive either 50, 100, or 200 mg of OPT-80 orally every 12 h for 10 days as treatment for mild to moderately severe CDI. OPT-80 was well tolerated by all subjects. Plasma concentrations were below the lower limit of quantitation in almost one-half of patients and typically ≤20 ng/ml across the dose range; the mean fecal concentrations exceeded the MIC at which 90% of the isolates tested are inhibited by 2,000- to 10,000-fold with increasing dosages. Resolution of diarrhea within 10 days was achieved in 10/14 patients (71%), 12/15 patients (80%), and 15/16 patients (94%), and the median time to resolution of diarrhea was reduced from 5.5 to 3.0 days with increasing dosages. Across all groups, the clinical cure rate, which was defined as resolution of diarrheal disease without the need for further treatment, was 41/45 patients (91%). Recurrence of CDI at ~1 month after treatment was observed in two (5%) patients, one each in the 100-mg and 400-mg groups. The apparent high clinical response, good tolerance, low recurrence rate, and more-complete and rapid symptom control with the highest dosage support the selection of the 200-mg twice-daily dose for further clinical development of OPT-80 for treatment of CDI.

* Corresponding author. Mailing address: AGW5, Infection Prevention & Control, Foothills Medical Center, 1403 29th St. N.W., Calgary, Alberta T2N 2T9, Canada. Phone: (403) 944-4766. Fax: (403) 944-2484. E-mail: louie{at}ucalgary.ca

{triangledown} Published ahead of print on 27 October 2008.

Antimicrobial Agents and Chemotherapy, January 2009, p. 223-228, Vol. 53, No. 1
0066-4804/09/$08.00+0     doi:10.1128/AAC.01442-07
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sullivan, K. M, Spooner, L. M (2010). Fidaxomicin: A Macrocyclic Antibiotic for the Management of Clostridium difficile Infection. The Annals of Pharmacotherapy 44: 352-359 [Abstract] [Full Text]  
  • Williams, O. M., Spencer, R. C. (2009). The management of Clostridium difficile infection. Br Med Bull 91: 87-110 [Abstract] [Full Text]  
  • Louie, T. J., Emery, J., Krulicki, W., Byrne, B., Mah, M. (2009). OPT-80 Eliminates Clostridium difficile and Is Sparing of Bacteroides Species during Treatment of C. difficile Infection. Antimicrob. Agents Chemother. 53: 261-263 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»